The human intestine has a vast variety of microorganisms, and their balance is dependent
on several factors. Antibiotics affect microfloral balance and allow naturally opportunistic
organisms to multiply. Azithromycin is the most widely used macrolide antibiotic,
active against a wide number of pathogens including Pseudomonas aeruginosa and Staphylococcus
aureus. It is currently used in the treatment of cystic fibrosis patients. The use
of probiotics has advantages in gastrointestinal conditions, including infectious
diarrhea and imbalance due to antibiotic use. In this research, the effect of azithromycin
on the intestinal microbiota of Sprague Dawley rats and the role of Lactobacillus
acidophilus in the restoration of the balance by employing molecular and cultural
techniques was investigated. PCR with universal primers targeting the V3 region of
the 16S rRNA gene followed by DGGE was used to characterize the overall intestinal
microbiota composition. Cultivable fecal bacteria count using microbiological media
and semi-quantitative PCR with group-specific primers were also utilized to analyze
the effects of antibiotic and probiotic on microflora. We found that the total amount
of 16S rRNA gene and fecal aerobic bacterial count was reduced following azithromycin
administration along with elimination of non-pathogenic Escherichia coli, but it was
restored by the use of the probiotic. The results from PCR with group-specific primers
showed that Bacteroides sp was present in the control and probiotic groups, but it
was nearly eliminated in the antibiotic group. Moreover, semi-quantitative PCR revealed
that the numbers of Enterobacteriaceae were nearly the same in the probiotic group
and decreased in the antibiotic group, while Bifidobacterium was significantly increased
in the probiotic group and decreased in the antibiotic group (P < 0.05) as compared
with that in the control group. Azithromycin-induced dysbiosis can result in prolonged
deleterious effects on the host. The present study revealed that the use of lactic
acid bacteria particularly L. acidophilus helped to restore intestinal microfloral
balance.

We recently reported that chemical clearance (CC) of acid gastroesophageal reflux
(AGER) is relatively prolonged in children with cystic fibrosis (CF). Disparity in
CC values within our CF cohort sparked curiosity as to what CC looks like in infants
and children with AGER in the physiologic range. AIM:: To assess CC in infants and
children with normal AGER.Impedance-pH tracings from our database for infants (≤12 months) and children (>12
months-18 years) were manually scanned for two-phase AGER episodes. Tracings were
excluded for subjects who had AGER Indices >3% (children) or >6% (infants), had positive
GER-symptom associations, were on anti-reflux medications, had a fundoplication, or
had impedance studies shorter than 18 h. In addition to medians (25-75% IQR), we calculated
the 95 percentile for CC duration and the 5 percentile for CC rate.Two-phase AGER episodes were detected in 44 infants and 60 children. Median CC duration
was 64.3 s (51.0-91.6 s) for infants and 37.5 s (27.7-52.4 s) for children. Median
CC rate was 0.0622 pH units/sec (PU/s) (0.0354-0.0946 PU/s) for infants and 0.0928 PU/s
(0.0631-0.2057 PU/s) for children. CC duration at the 95 percentile was 148.5 s for
infants and 114.4 s for children. CC rate at the 5 percentile was 0.0088 PU/s for
infants and 0.0465 PU/s for children.We report reference values for CC in infants and children who have normal acid reflux.
These values should not be used as "cut-off values" because they were derived from
infant and children cohorts that did not include individuals with intermediate AGER.

Twenty-five years after the cystic fibrosis (CF) gene identification, this discovery
actually begins to benefit to patients. Increasing our knowledge on CFTR biology,
as well as technical progress made in order to screen for new drugs have made therapeutic
strategies move an important step forward. It is likely that in the forthcoming years,
the panel of molecules available for CF patients will be larger, with new activators
and potentiators. The disease by itself may consequently change in its natural history.
CF is an example of the so-called personalized medicine, aiming to fit treatment according
to patient's genetic background. Ongoing clinical trials may enlarge the actually
limited eligible number of CF patients for new drugs such as ivacaftor. Beyond this
exciting and promising new therapeutic approach, one may not push symptomatic treatments
on the side. Improvements have been made for inhaled antibiotics administration, aiming
to simplify patient's life; clinical trials using new molecules able to liquefy mucus
or with anti-inflammatory properties are actually underway. One important next step
in the care for CF will be to design and conduct early intervention trials in CF infants.
Newborn screening program have been widely implanted around the word, and cohorts
studies have shown that both functional and structural abnormalities occurred very
early, making the therapeutic window of opportunity tight.

Lung transplantation (LT) is now considered as an excellent treatment option for selected
patients with end-stage pulmonary diseases, such as COPD, cystic fibrosis, idiopathic
pulmonary fibrosis, and pulmonary arterial hypertension. The 2 goals of LT are to
provide a survival benefit and to improve quality of life. The 3-step decision process
leading to LT is discussed in this review. The first step is the selection of candidates,
which requires a careful examination in order to check absolute and relative contraindications.
The second step is the timing of listing for LT; it requires the knowledge of disease-specific
prognostic factors available in international guidelines, and discussed in this paper.
The third step is the choice of procedure: indications of heart-lung, single-lung,
and bilateral-lung transplantation are described. In conclusion, this document provides
guidelines to help pulmonologists in the referral and selection processes of candidates
for transplantation in order to optimize the outcome of LT.

With the increasing resistance to antibiotics among common bacterial pathogens, challenges
associated with the use of fluoroquinolones (FQs) in paediatrics have emerged. The
majority of FQs have favourable pharmacokinetic properties, although these properties
can differ in children compared with adults. Moreover, all FQs have broad antimicrobial
activity both against Gram-positive and Gram-negative bacteria. However, only some
FQs for which adequate studies are available have been approved for use in children
in a limited number of clinical situations owing to the supposed risk of development
of severe musculoskeletal disorders, as demonstrated in juvenile animals. Recent short-
and long-term evaluations appear to indicate that, at least for levofloxacin, this
risk, if present at all, is marginal. This marginal risk could lead to more frequent
use of FQs in children, even to treat diseases for which several other drugs with
documented efficacy, safety and tolerability are considered the first-line antibiotics.
However, for most of the FQs, adequate long-term studies of safety are not available.
This indicates that the use of FQs should be limited to selected respiratory infections
(including tuberculosis), exacerbation of lung disease in cystic fibrosis, central
nervous system infections, enteric infections, febrile neutropenia, as well as serious
infections attributable to FQ-susceptible pathogen(s) in children with life-threatening
allergies to alternative agents. When considering diseases that could benefit from
the use of FQs, particular attention must be paid to the choice of drug and its dosage,
considering that not all of the FQs have been evaluated in different diseases.

This article is the summary of a workshop, which took place in November 2013, on the
roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed
that lower airways were sterile in healthy individuals. However, it has long been
acknowledged that microorganisms could be identified in distal airway secretions from
patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF
bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway
diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms
were sometimes considered as infectious agents that triggered host immune responses
and contributed to disease onset and/or progression; alternatively, microorganisms
were often considered as colonisers, which were considered unlikely to play roles
in disease pathophysiology. These concepts were developed at a time when the identification
of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms
cannot be cultured using conventional methods, and the use of novel culture-independent
methods that rely on the identification of microorganism genomes has revealed that
healthy distal airways display a complex flora called the airway microbiota. The present
article reviews some aspects of current literature on host-microbe (mostly bacteria
and viruses) interactions in healthy and diseased airways, with a special focus on
distal airways.

Although recent studies have begun to elucidate how airway microbial community structure
relates to lung disease in cystic fibrosis (CF), microbial community activity and
the host's response to changes in this activity are poorly understood. Metabolomic
profiling provides a means to investigate microbial activity and human cell activity
within diseased airways. However, variables in sample storage and shipping likely
affect downstream analyses and standards for sample handling are lacking.We assessed the impact of sample storage conditions on liquid chromatography mass
spectrometry analysis of CF sputum samples.Significant changes in global metabolomic profiles occurred in samples stored at room temperature or at 4°C for longer than one day. Untargeted metabolomic profiles were stable in sputum samples stored at -20°C or -80°C for at least 28days. Quorum sensing molecules and phenazines, both considered important to the in vivo activity of Pseudomonas during airway infection, were detected after sample storage at room temperature for five days.Sputum samples can be stored at -20°C or -80°C for weeks with minimal effect on global metabolomic profiles. This observation provides guidance in designing metabolomic studies that have the potential to deepen our understanding of how airway microbial communities impact lung disease progression in CF.